Effectiveness and safety of drugs for obesity

Dear Editor
A significant progress has been made in the last half-century in the management of disorders like depression, anxiety, type -2 diabetes, hypertension, arterial fibrillation, psoriasis, osteoarthritis, male infertility that are closely related with excess body weight, however, the treatment of obesity itself has proven largely resistant to therapy, with anti-obesity medications (AOMs) often delivering insufficient efficacy and dubious safety.(1) As lifestyle and behavioral interventions provide moderate efficacy, obesity treatment protocols are to be modified by adding surgical interventions like Bariatric surgery that represents the most effective approach to weight loss.(2)

A plethora of medicines that have been investigated in obesity include agents as diverse as mitochondrial uncoupler, sympathomimetics, serotonergic agonists, lipase inhibitors, cannabinoid receptor antagonists and gastrointestinal-derived peptides. (3,4,5,6,7), however question mark on the safety and efficacy of these drugs still exists.

A recent study has provided valuable insight into the potential health benefits of traditional herbal remedies as antiobesity agent however recommendations suggest use of these products under qualified supervision. (8)
According to the National Heart, Lung, and Blood Institute guideline of “Pharmacological Management of Obesity”, moderate exercise is one of the best tools along with anti-obesity therapy to overcome complications of obesity. (9)

It has been well established that personalized tailored medicines are required for most of the disorders specially those accompanying co morbidities. There is a need to apply principals of Ayurveda/traditional medicine/regional therapy modules for selection of antiobesity agents based on the personalized genetic makeup of an individual for a successful antiobesity regimen.(10)

With increasing technology allowing deeper phenotyping of individuals, increased sophistication in the analysis of big data and the emergence of new treatments, it is possible that precision medicine for obesity will eventuate. Standardizing these tools and outcome measures to enable pooling of datasets (11), and increased sophistication in the analysis of big data, will undoubtedly aid in identifying more consistent predictors of response
One of the strategies for long-term obesity control is that anti-obesity medications should be tailored for specific patients depending on their chronic conditions, comorbidities, and preferences. For now, a personalized approach that takes into account the person’s context, preferences, comorbidities and contraindications is recommended.

1.Müller TD, Blüher M, Tschöp MH, DiMarchi RD. Anti-obesity drug discovery: advances and challenges. Nature Reviews Drug Discovery. 2022 Mar;21(3):201-23.
2.Carlsson LM, Sjöholm K, Jacobson P, Andersson-Assarsson JC, Svensson PA, Taube M, Carlsson B, Peltonen M. Life expectancy after bariatric surgery in the Swedish obese subjects study. New England Journal of Medicine. 2020 Oct 15;383(16):1535-43.
3.Khera R, Murad MH, Chandar AK, Dulai PS, Wang Z, Prokop LJ, Loomba R, Camilleri M, Singh S. Association of pharmacological treatments for obesity with weight loss and adverse events: a systematic review and meta-analysis. Jama. 2016 Jun 14;315(22):2424-34.
4. Tainter ML, Stockton AB, Cutting WC. Use of dinitrophenol in obesity and related conditions: a progress report. Journal of the American Medical Association. 1933 Nov 4;101(19):1472-5.
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6.Després JP, Golay A, Sjöström L. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. New England Journal of Medicine. 2005 Nov 17;353(20):2121-34.
7.Pi-Sunyer FX, Aronne LJ, Heshmati HM, Devin J, Rosenstock J, RIO-North America Study Group FT. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. Jama. 2006 Feb 15;295(7):761-75.
8. Hawash M, Jaradat N, Salhi NA, Shatreet B, Asbah AA, Hawash YH. Assessing the therapeutic potential and safety of traditional anti-obesity herbal blends in Palestine. Scientific Reports. 2024 Jan 22;14(1):1919.
9.Apovian CM, Aronne LJ, Bessesen DH, McDonnell ME, Murad MH, Pagotto U, Ryan DH, Still CD. Pharmacological management of obesity: an endocrine Society clinical practice guideline. The Journal of Clinical Endocrinology & Metabolism. 2015 Feb 1;100(2):342-62.
10.Hocking S, Sumithran P. Individualised prescription of medications for treatment of obesity in adults. Reviews in Endocrine and Metabolic Disorders. 2023 Oct;24(5):951-60.
11.Alligier M, Barrès R, Blaak EE, Boirie Y, Bouwman J, Brunault P, Campbell K, Clément K, Farooqi IS, Farpour-Lambert NJ, Frühbeck G. OBEDIS core variables project: European expert guidelines on a minimal core set of variables to include in randomized, controlled clinical trials of obesity interventions. Obesity facts. 2020 Jan 16;13(1):1-28.